The overall objective of this proposal is to participate as a Radiotherapy Center in a multi-institutional series of Phase I, II, and Phase III clinical trials evaluating 3-D conformal radiotherapy and dose escalation for the treatment of advanced prostate cancer. Prostate cancer is the second most common cancer among men and, when present in its early stages, is often controlled well with either surgery or radiotherapy. In advanced cases, local recurrence is more frequent after radiotherapy and surgery is often not an alternative. As part of a multi-institutional group, a series of trials will be designed to test the hypothesis that an increased dose of radiotherapy can be delivered tolerably and with more effectiveness through the use of three-dimensional treatment planning. This project plans to enroll patients with large prostate cancers into a dose escalation trial to determine the maximum tolerated dose. The exact details of the protocol will be determined by the Executive Committee. Appended to this application is a detailed proposal for such a protocol. Briefly, Stage B-2, C (T2b, T2c, T3, T4) tumors would be entered and treated with gradually increasing doses of radiotherapy to determine the maximum tolerated dose. Data, including dose volume histogram analysis, will be supplied to an Operations Center for data on radiation-induced damage to normal tissues. Once the maximal tolerated dose has been reached, then a Phase III trial will be designed to test the efficacy of 3-D conformal radiotherapy. The University of Michigan is ideally suited to participate as a Radiotherapy Center in a national radiotherapy trial for 3-D dose escalation in prostate cancer due to: 1) its commitment to participate in multi-institutional protocols as evidenced by its involvement with SWOG; 2) its superior capability in 3-D treatment planning, treatment delivery and 3-D conformal prostate treatment; 3) its expertise in evaluation and QA of 3-D conformal treatment; 4) the availability of qualified and experienced support personnel; 5) the availability of patients to be entered in the trials; 6) the availability and experience of personnel to administer radiotherapy trials, and 7) its capability to exchange digital treatment planning data as demonstrated by previous involvement in a national treatment planning contract.